OBJECTIVE:
To determine if sorafenib is associated with an improved 4-month
probability of progression-free survival, using radiographic and
clinical criteria alone, in patients with metastatic
castration-resistant prostate cancer. Secondary endpoints included
pharmacokinetics, toxicity analysis and overall survival.PATIENTS AND
METHODS: The study was an open-label, phase II, two-stage design,
focusing on the results from the second stage, as criteria for
progression were modified after completing the first stage. Sorafenib
was given at a dose of 400 mg orally twice daily in 28-day cycles.
Clinical and laboratory assessments were done every 4 weeks, and
radiographic scans were obtained every 8 weeks.RESULTS: Twenty-four
patients were accrued in the second stage; the median (range) age was
66 (49-85) years, the on-study prostate-specific antigen level was
68.45 (5.8-995) ng/mL, the Gleason score 8 (6-9) and Eastern
Cooperative Oncology Group status 1 (in 17 patients). Of the 24
patients, 21 had previous chemotherapy with docetaxel. All patients had
bony metastases, either alone (in 11) or with soft-tissue disease (in
13). One patient had a partial response; 10 patients had stable disease
(median duration 18 weeks, range 15-48). At a median potential
follow-up of 27.2 months, the median progression-free survival was 3.7
months and the median overall survival was 18.0 months. For the whole
trial of 46 patients the median survival was 18.3 months. Most frequent
toxicities included hand-foot skin reaction (grade 2 in nine patients,
grade 3 in three), rash, abnormalities in liver function tests, and
fatigue.CONCLUSIONS: Sorafenib has moderate activity as a second-line
treatment for metastatic castration-resistant prostate cancer.